Advanced three-dimensional graphics are essential to the visualization and analysis of molecular structure. I am using the advanced molecular graphics capabilities of the Computer Graphics Laboratory at UCSF to aid in the crystallographic structure determinations of a number of complexes of thymidylate synthase (TS) with putative anti-cancer drug lead compounds. TS is a crucial target for anti-cancer drug design since it exists as the sole biosynthetic source of dTMP, a direct precursor to the DNA base thymine (T). Since cells which are undergoing division are rapidly synthesizing DNA, cancer cells in particular exhibit an elevated demand for this base. The ability to inhibit or effectively stop the production of this nucleotide base would therefore be an efficacious means of controlling the spread of cancers in the body. With data of several TS-drug lead complexes in hand, I am now in the position of requiring intensive, high-quality computer graphics to visualize these complexes in three dimensions to analyze the protein-ligand molecular interactions. This visualization will enable me to predict appropriate modifications to the ligands which will enhance these interactions and lead to more effective complexes. In the past year, we have already moved from moderately weak complexes (Kd ~ 100 uM) to moderate complexes (Kd <= 1 uM) to high-affinity complexes (Kd ~ 10 pM) solely on the basis of visualized molecular graphics. This has been done primarily through the use of MidasPlus (UCSF), CHAIN (Baylor), O (Aarhus), and the Cambridge Structural Database.